This patent specification relates generally to medical monitoring and medical resuscitative systems and methods. More specifically, it relates to an adaptive neural stimulator system and method for the treatment of traumatic brain injury and the often resulting persistent vegetative state or xe2x80x9ccoma,xe2x80x9d and to the treatment of other brain dysfunctions such as movement disorders, and psychiatric disorders such as depression, schizophrenia, and anxiety disorders. The system stimulates and modifies parameters of stimulation based upon the outcome of comparing the patient""s present state with a reference state with the intention of improving the overall functional state of the patient. The stimulation can be electrical, pharmacological, or both.
The term xe2x80x9ccomaxe2x80x9d is used to describe a human patient""s state wherein the patient is unconscious and immobile and does not respond to intense sensory stimuli, for example, yelling. A xe2x80x9cdeep comaxe2x80x9d occurs when this state lasts for more than 1 week. Although coma may result from several causes including drug reactions or cardiovascular stroke, it is often due to head injury, for example, head trauma due to an automobile accident.
Historically, recovery from coma has been demonstrated primarily in laboratory animals. Early studies in cats showed that functional disconnection of the reticular formation from the rest of the central nervous system (CNS) resulted in a loss of consciousness, implicating this region as responsible for the state of CNS arousal. Subsequent research (Adametz J H, Recovery of functioning in cats with rostral reticular lesions, J of Neurosurgery, 1959 (16), p. 85-97) showed that if the reticular region was destroyed in consecutive steps, rather than all at once, and the brain was given the opportunity to reorganize itself, the animals would not lose consciousness. A characteristic of the brain that enables it to respond to the insult that resulted in coma is neural plasticity which occurs when the functions of a damaged region of neural tissue is taken over by other areas that normally did not previously play a role in that particular function. Some patients are able to regain consciousness after being in a coma because the brain can respond to traumatic injury by using such adaptive capacities as functional and structural reorganization, upregulation or downregulation of a neural response to an event, and the establishment of new functional and structural connections by means of collateral sprouting and compensatory synaptogenesis.
Recent evidence indicates that direct electrical stimulation of the human brain can be effective in the reversal of persistent vegetative state (PVS) resulting from traumatic injury or stroke (Hassler R, et al., EEG and clinical arousal induced by bilateral long-term stimulation of pallidal systems in traumatic vigil coma. Electroencephalogr Clin Neurophysiol. 1969 September; 27(7): 689-690. Cohadon F, et al, Deep cerebral stimulation in patients with post-traumatic vegetative state. Neurochirurgie. 1993; 39(5): 281-292. Deliac P, et al., Electrophysiological development under thalamic stimulation of post-traumatic persistent vegetative states. Neurochirurgie. 1993; 39(5): 293-303. Cohadon F, et al., Recovery of motor function after severe traumatic coma. Scand J Rehabil Med Suppl. 1988; 17: 75-85. Kanno T, et al. Effects of dorsal column spinal cord stimulation (DCS) on reversibility of neuronal functionxe2x80x94experience of treatment for vegetative states. Pacing Clin Electrophysiol. 1989 April; 12(4 Pt 2): 733-738. Kanno T, et al Neurostimulation for patients in vegetative status. Pacing Clin Electrophysiol. 1987 January; 10(1 Pt 2): 207-208. Tsubokawa T, et al. Deep-brain stimulation in a persistent vegetative state: follow-up results and criteria for selection of candidates. Brain Inj. 1990 October; 4(4): 315-327. Katayama Y, et al. Coma induced by cholinergic activation of a restricted region in the pontine reticular formationxe2x80x94a model of reversible forms of coma. Neurol Med Chir (Tokyo). 1986 January; 26(1): 1-10.) or in improving motor control in patients with movement disorders such as Parkinson""s Disease (Limousin P, et al., Effect of parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation. Lancet. Jan. 14, 1995; 345(8942): 91-95. Limousin P, et al Bilateral subthalamic nucleus stimulation for severe Parkinson""s disease. Mov Disord. 1995 September; 10(5): 672-674. Pollak P, et al., External and implanted pumps for apomorphine infusion in parkinsonism. Acta Neurochir Suppl (Wien). 1993; 58: 48-52. Pollak P, et al., Long-term effects of chronic stimulation of the ventral intermediate thalamic nucleus in different types of tremor. Adv Neurol. 1993; 60: 408-413.). There is also evidence that electrophysiological (EEG or ERP), electromyographic (EMG), neurochemical (CSF metabolites), peripheral (circulating beta-endorphin levels), radiological (CT scan, MRI) and clinical (Pupillary Light Reflex, Glasgow Coma Scale) measures may aid in providing useful selection criteria for patients who may be likely to successfully respond to direct brain stimulation (DBS) treatment. These measures may also offer ways to monitor the efficiency of acute or chronic DBS treatment. Since there are perhaps 2,000,000 cases of traumatic brain injury each year in the United States, with a substantial percentage leading to a persistent vegetative state or xe2x80x9ccomaxe2x80x9d, successful coma treatment would be of significant clinical utility, decreasing mortality and morbidity.
Instruments for direct electrical brain stimulation are currently available from several companies (Medtronic, Neuromed, Cochlear Corp, Advanced Bionics). These devices are in clinical use and often rely on systems chronically implanted into the brain or peripheral sites. U.S. Pat. No. 4,735,204 (referred to herein as xe2x80x9cthe ""204 patentxe2x80x9d) discusses a system for controlling a neural stimulation device that is implanted in the epidural space along the spine and is used to block ascending pain signals in chronic pain. The amount of pain may change over time depending upon the patient""s activity level or position, and the ""204 patent discusses how the level of current supplied to an implanted stimulation electrode is modified, within certain acceptable limits, through the use of externally applied magnetic signals, thereby avoiding a visit to a medical facility. In the ""204 patent the optimal level of stimulation is chosen by the patient by a criterion where the patient again attains comfort. U.S. Pat. No. 5,342,409 discusses a chronically implanted position responsive neurostimulator which is useful in the treatment of cases with chronic intractable pain, various movement disorders, and lack of bowel and bladder control, and in which the stimulation parameters are programmed into a stimulation controller by professional personnel via transcutaneous RF telemetry signals. U.S. Pat. No. 4,592,359 discusses a multi-channel implantable neural stimulator which functions as an auditory prosthesis. The proposed system includes a transmitter and a chronically implantable receiver and an efficient transmitted data format which both transmits data and induces a charge on the implanted stimulator. U.S. Pat. No. 5,716,377 (""377 patent), discusses a method of treating movement disorders by brain stimulation which is based upon an algorithm in which a control signal is used to increase or decrease neurostimulation parameters within a predetermined range of safety. The ""377 patent does not teach a method of individually changing neurostimulation parameters such as is possible using a multiple lead stimulator. Further, the ""377 method and system rely on a tremor/no tremor criteria, rather than computing a score and/or storing a score, such as a Z-score, discriminant probability, or multivariate index, in order to compare different amounts of tremor which may be below a target threshold. All sensed data which indicate that the current state of the patient is below a certain threshold are treated as equal.
While the technology discussed above can be of considerable medical utility, none of the described approaches utilizes a systematic, statistical, and medically meaningful method for determining the stimulation parameters in order to optimize efficacy of stimuli to be ultimately used in treatment. Accordingly, an object of the adaptive brain stimulation (ABS) system and method disclosed in this patent specification is to greatly improve the treatment of central nervous system pathology by relying on statistically significant and medically meaningful criteria for choosing and modifying as needed a specified program of simulation.
A further object of the system and method disclosed herein is to utilize an ABS that controls multiple stimulation devices that are implanted in more than one brain region (e.g., a first brain region and a second brain region), and which stimulate these regions according to a set of parameters that produce functional or structural recovery which enables the patient to overcome unwanted effects resulting from traumatic brain injury, stroke, or other brain disorder or dysfunction. The brain stimulation may be pharmacological, electrical, or both, as described in greater detail below.
In one exemplary and non-limiting embodiment disclosed herein, an adaptive brain stimulation system and method aid in the rehabilitation of patients with traumatic brain injury which has resulted in a persistent vegetative state, or other brain dysfunction. After a direct brain stimulator is implanted in a brain region of a patient, the patient is stimulated according to a set of stimulation parameters. A present state is measured and compared to a reference state. If the comparison meets a set of criteria, then the stimulation is producing a desired effect and a positive outcome is said to have occurred resulting in a continuation of stimulation according to a current or similar set of stimulation parameters. If, however, after a specified amount of time or number of attempts, the comparison fails to meet a set of criteria then new sets of stimulation parameters are selected and subsequently tested until a positive outcome occurs.
In an alternative embodiment, in the case of a positive outcome a second set of DBS""s which is at another brain region may also be stimulated by a specified reinforcement schedule. If this second brain region is related to reward, then the brain is reinforced for producing a response that succeeds in meeting a criteria. There is a substantial body of literature on classical and operant conditioning that discusses such positive reinforcement.
The ABS system comprises a feedback loop that provides stimulation to a patient based upon statistical and medical criteria. In actual practice the system includes electronics, sources of power, amplifiers, stimulators, and appropriate connection and communication between functionally related components. External components can be under control of a personal computer (PC), and internal components are controlled by micro-electronics. As known in the art, and as described in the above cited material, current technology can allow the ABS system to be almost completely implanted or it may have a relatively large number of its components located external to the patient. If the ABS is located internally, it can contain both communication circuits for sending and receiving signals to its external components and a long-lasting replaceable or rechargeable power supply which can be recharged via induction or by radio frequency transmission. Since the ABS system is a medical device, it should meet patient safety standards by including protection of the patient from electrical surges and runaway feedback, and can includes the necessary hardware and software subroutines to perform appropriate diagnostic checks to ensure correct functioning.
After the patient regains consciousness by returning from the coma or manifests another desired improvement by recovering from a dysfunctional state, the ABS system can be implanted into a patient, or remain implanted, and aid in the subsequent maintenance of the normal state.